Immunization with a multisubunit vaccine considerably reduces establishment of infective larvae in a rodent model of Brugia malayi

Shrivastava, Nidhi; Singh, Prashant Kumar; Nag, Jeetendra Kumar; Kushwaha, Sapana; Misra‐Bhattacharya, Shailja

doi:10.1016/j.cimid.2013.05.003

Cited by 13 publications

(13 citation statements)

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“…Bm-TPP and BmAF-Myo earlier showed good immunoprophylactic efficacy in experimental animal models in our laboratory [24–27]. We also cloned and characterized two Wolbachia proteins, Wol Tl IF-1 and w Bm-LigA [28–30].…”

Section: Discussionmentioning

confidence: 99%

“…Both have been cloned and characterized by us [22, 23]. Brugia malayi TPP (Bm-TPP) and BmAF-Myo both show cross-reactivity with bancroftian human sera and provide significant protection against infective larval challenge in experimental rodent models [24–27]. Wolbachia translation initiation factor-1 (Wol Tl IF-1) is an excretory-secretory protein that also elicits protective immunity in rodent model [28].…”

Section: Introductionmentioning

confidence: 99%

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Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

et al. 2017

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BackgroundIn the past, immune responses to several Brugia malayi immunodominant antigens have been characterized in filaria-infected populations; however, little is known regarding Wolbachia proteins. We earlier cloned and characterized few B. malayi (trehalose-6-phosphate phosphatase, Bm-TPP and heavy chain myosin, BmAF-Myo) and Wolbachia (translation initiation factor-1, Wol Tl IF-1 and NAD+-dependent DNA ligase, wBm-LigA) proteins and investigated the immune responses, which they triggered in animal models. The current study emphasizes on immunological characteristics of these proteins in three major categories of filarial endemic zones: endemic normal (EN, asymptomatic, amicrofilaraemic; putatively immune), microfilariae carriers (MF, asymptomatic but microfilaraemic), and chronic filarial patients (CP, symptomatic and mostly amicrofilaraemic).MethodsImmunoblotting and ELISA were carried out to measure IgG and isotype antibodies against these recombinant proteins in various clinical categories. Involvement of serum antibodies in infective larvae killing was assessed by antibody-dependent cellular adhesion and cytotoxicity assay. Cellular immune response was investigated by in vitro proliferation of peripheral blood mononuclear cells (PBMCs) and reactive oxygen species (ROS) generation in these cells after stimulation.ResultsImmune responses of EN and CP displayed almost similar level of IgG to Wol Tl IF-1 while other three proteins had higher serum IgG in EN individuals only. Specific IgA, IgG1, IgG3 and IgM to Bm-TPP were high in EN subjects, while BmAF-Myo additionally showed elevated IgG2. Enhanced IgA and IgG3 were detected in both EN and CP individuals in response to Wol Tl IF-1 antigen, but IgG1 and IgM were high only in EN individuals. wBm-LigA and BmAF-Myo exhibited almost similar pattern of antibody responses. PBMC isolated from EN subjects exhibited higher proliferation and ROS generation when stimulated with all three proteins except for Wol Tl IF-1.ConclusionsOverall, these findings display high immunogenicity of all four proteins in human subjects and revealed that the EN population was exposed to both B. malayi and Wolbachia proteins simultaneously. In addition, immune responses to Wol Tl IF-1 suggest possible role of this factor in Wolbachia-induced pathological responses while immune responses to other three proteins suggest that these can be explored further as vaccine candidates.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1963-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

et al. 2017

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“…Multivalent vaccines have been successfully developed against the filarial worm Brugia malayi (Anand et al, 2011; Joseph and Ramaswamy, 2013; Shrivastava et al, 2013) and immunization of calves with a multivalent vaccine against Onchocerca ochengi reduced the development of patency as determined by a decrease in the number of animals with microfilariae in the skin (Makepeace et al, 2009). It was hypothesized that immunizing mice against O. volvulus with two or three of the protective antigens would induce elevated levels of protective immunity.…”

Section: Discussionmentioning

confidence: 99%

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

Hess

Zhan

Bonne-Année

et al. 2014

International Journal for Parasitology

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Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunization protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans.

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“…The recombinant protein was expressed as described earlier [10]. In brief, bm-myo gene was cloned into expression vector pET 28a which was transformed in competent BL21 (DE3) E .…”

Section: Methodsmentioning

confidence: 99%

“…We earlier identified B . malayi recombinant heavy chain myosin (Bm-Myo) as potential prophylactic antifilarial vaccine candidate in a single and cocktail vaccine formulation [4, 10]. DNA based vaccines are relatively simple, inexpensive to produce [11] and have been shown to confer effective protection against several pathogens by inducing humoral and cellular immune responses in the immunized host.…”

Section: Introductionmentioning

confidence: 99%

Immunization with Brugia malayi Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against B. malayi Infection in Mastomys coucha

2016

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The current control strategies employing chemotherapy with diethylcarbamazine, ivermectin and albendazole have reduced transmission in some filaria-endemic areas, there is growing interest for complementary approaches, such as vaccines especially in light of threat of parasite developing resistance to mainstay drugs. We earlier demonstrated recombinant heavy chain myosin of B. malayi (Bm-Myo) as a potent vaccine candidate whose efficacy was enhanced by heterologous DNA prime/protein boost (Myo-pcD+Bm-Myo) vaccination in BALB/c mice. BALB/c mouse though does not support the full developmental cycle of B. malayi, however, the degree of protection may be studied in terms of transformation of challenged infective larvae (L3) to next stage (L4) with an ease of delineating the generated immunological response of host. In the current investigation, DNA vaccination with Bm-Myo was therefore undertaken in susceptible rodent host, Mastomys coucha (M. coucha) which sustains the challenged L3 and facilitates their further development to sexually mature adult parasites with patent microfilaraemia. Immunization schedule consisted of Myo-pcD and Myo-pcD+Bm-Myo followed by B. malayi L3 challenge and the degree of protection was evaluated by observing microfilaraemia as well as adult worm establishment. Myo-pcD+Bm-Myo immunized animals not only developed 78.5% reduced blood microfilarial density but also decreased adult worm establishment by 75.3%. In addition, 75.4% of the recovered live females revealed sterilization over those of respective control animals. Myo-pcD+Bm-Myo triggered higher production of specific IgG and its isotypes which induced marked cellular adhesion and cytotoxicity (ADCC) to microfilariae (mf) and L3 in vitro. Both Th1 and Th2 cytokines were significantly up-regulated displaying a mixed immune response conferring considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccination method against LF.

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Immunization with a multisubunit vaccine considerably reduces establishment of infective larvae in a rodent model of Brugia malayi

Cited by 13 publications

References 46 publications

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Humans from Wuchereria bancrofti endemic area elicit substantial immune response to proteins of the filarial parasite Brugia malayi and its endosymbiont Wolbachia

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

Immunization with Brugia malayi Myosin as Heterologous DNA Prime Protein Boost Induces Protective Immunity against B. malayi Infection in Mastomys coucha

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